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Vol. 18, Issue 4, 1272-1281, April 2007

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Junction Protein Shrew-1 Influences Cell Invasion and Interacts with Invasion-promoting Protein CD147

Alexander Schreiner^*, Mika Ruonala, Viktor Jakob^*, Jan Suthaus, Eckhard Boles, Fred Wouters, and Anna Starzinski-Powitz^*

*Institute of Cell Biology and Neuroscience, Johann Wolfgang Goethe University of Frankfurt, D-60323 Frankfurt am Main, Germany; European Neuroscience Institute Göttingen, D-37077 Göttingen, Germany; Institute of Biochemistry, Christian-Albrechts-Universität Kiel, D-24098 Kiel, Germany; and Institute of Molecular Biosciences, Johann Wolfgang Goethe University of Frankfurt, D-60438 Frankfurt am Main, Germany

Submitted July 27, 2006; Revised December 6, 2006; Accepted January 22, 2007
Monitoring Editor: Asma Nusrat

Shrew-1 was previously isolated from an endometriotic cell line in our search for invasion-associated genes. It proved to be a membrane protein that targets to the basolateral membrane of polarized epithelial cells, interacting with E-cadherin–catenin complexes of adherens junctions. Paradoxically, the existence of adherens junctions is incompatible with invasion. To investigate whether shrew-1 can indeed influence cellular invasion, we overexpressed it in HT1080 fibrosarcoma cells. This resulted in enhanced invasiveness, accompanied by an increased matrix metalloprotease (MMP)-9 level in the supernatant, raising the question about the role of shrew-1 in this process. Logic suggested we looked for an interaction with CD147, a known promoter of invasiveness and MMP activity. Indeed, genetics-based, biochemical, and microscopy experiments revealed shrew-1– and CD147-containing complexes in invasive endometriotic cells and an interaction in epithelial cells, which was stronger in MCF7 tumor cells, but weaker in Madin-Darby canine kidney cells. In contrast to the effect mediated by overexpression, small interfering RNA-mediated down-regulation of either shrew-1 or CD147 in HeLa cells decreased invasiveness without affecting the proliferation behavior of HeLa cells, but the knockdown cells displayed decreased motility. Altogether, our results imply that shrew-1 has a function in the regulation of cellular invasion, which may involve its interaction with CD147.

Address correspondence to: Anna Starzinski-Powitz (starzinski-powitz{at}em.uni-frankfurt.de)

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